Cytokines and growth factors play critical roles in normal homeostasis of immune functions. TGF-beta1 is the dominant negative regulator of inflammatory responses. We have earlier generated TGF-beta1 null mice that exhibit multifocal inflammation associated with increased adhesion of leukocytes to endothelium, aberrant expression of MHC class-I and -II antigens, and autoimmune manifestations similar to Sjogren syndrome. To delineate role of TGF-beta1 in aberrant MHC expression, TGF-beta1 null mice were generated in the MHC-I and MHC-II deficient backgrounds. TGF- beta1 X MHC-I null mice exhibit increased longevity associated with reduced inflammation, diminished autoimmune manifestations and significantly elevated myelopoiesis. Although the TGF-beta1 X MHC-II mice exhibited lack of inflammation and autoimmune response, they showed neonatal mortality associated with increased myelopoiesis and metaplasia. These results indicate a dominant role of TGF-beta1 in leukocyte maturation and function. Macrophage migration inhibitory factor (MIF) is a major protein constituent of the anterior pituitary gland released into the bloodstream during endotoxemia. For many years, MIF had been thought to be a T cell product associated with delayed-type hypersensitivity reactions. The identification of MIF as a pituitary "stress" hormone provides an important link in the regulation of systemic inflammatory responses by CNS. Additionally, there is a compelling evidence that suggests a strong link between MIF and cell cycle suggesting MIF as an inhibitor in G-0 phase. To dissect molecular roles of MIF, we have generated the mice heterozygous for the MIF locus. These mice are clinically normal and will be crossed to generate MIF null mice.